Journal of Cancer Research and Clinical Oncology

, Volume 133, Issue 9, pp 589–597

Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs)

  • Piotr Rutkowski
  • Zbigniew I. Nowecki
  • Maria Dębiec-Rychter
  • Urszula Grzesiakowska
  • Wanda Michej
  • Agnieszka Woźniak
  • Janusz A. Siedlecki
  • Janusz Limon
  • Anna Jerzak vel Dobosz
  • Michał Kąkol
  • Czesław Osuch
  • Włodzimierz Ruka
Original Paper

DOI: 10.1007/s00432-007-0202-4

Cite this article as:
Rutkowski, P., Nowecki, Z.I., Dębiec-Rychter, M. et al. J Cancer Res Clin Oncol (2007) 133: 589. doi:10.1007/s00432-007-0202-4

Abstract

The purpose

To analyze the outcomes of treatment and factors predicting effects of imatinib (IM) therapy in inoperable/metastatic gastrointestinal stromal tumors (GIST) CD117(+) patients.

Materials and methods

We identified 232 patients in a prospectively collected Clinical GIST Registry with advanced inoperable/metastatic GIST treated with IM 400-800 mg daily (129 males and 103 females and median age 56 years). Median follow-up time was 26 months.

Results

The estimated 3-year progression-free survival (PFS; calculated from the date of the start of IM) was 54% and median PFS was 40.5 months. The following factors significantly and negatively influenced PFS in univariate analysis: poor baseline World Health Organization (WHO) performance status ≥2 (P < 0.00001), tumor genotype indicating other than KIT exon 11 isoform (P = 0.005), baseline high neutrophils count (P < 0.00001), age <45 years at the diagnosis (P = 0.04), mitotic index >10/50 high-power fields (HPF) (P = 0.001), GIST histological type other than spindle-cell (P = 0.03), baseline low albumin level (P = 0.0005), low baseline hemoglobin level (P < 0.00001), and primary overtly malignant tumors (unresectable and/or metastatic lesions at presentation) (P = 0.05). We identified four factors negatively affecting PFS, statistically significant (P < 0.05) in multivariate analysis: baseline poor WHO performance status ≥2, high baseline neutrophils count (>5 × 109/l), tumor genotype indicating the presence of non-exon 11 KIT mutant and mitotic index >10/50 HPF.

Conclusions

We confirmed that many advanced GIST patients benefit from IM therapy for a prolonged time, although resistance to therapy is observed. We identified four independent biological factors influencing the PFS during long-term IM therapy.

Keywords

Gastrointestinal stromal tumorImatinibPrognosisPredictive factors

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Piotr Rutkowski
    • 1
  • Zbigniew I. Nowecki
    • 1
  • Maria Dębiec-Rychter
    • 2
  • Urszula Grzesiakowska
    • 3
  • Wanda Michej
    • 4
  • Agnieszka Woźniak
    • 5
  • Janusz A. Siedlecki
    • 6
  • Janusz Limon
    • 5
  • Anna Jerzak vel Dobosz
    • 6
  • Michał Kąkol
    • 7
  • Czesław Osuch
    • 8
  • Włodzimierz Ruka
    • 1
  1. 1.Department of Soft Tissue/Bone Sarcoma and MelanomaM. Sklodowska-Curie Memorial Cancer Center and Institute of OncologyWarsawPoland
  2. 2.Center for Human GeneticsUniversity of LeuvenLeuvenBelgium
  3. 3.Department of RadiologyM. Sklodowska-Curie Memorial Cancer Center and Institute of OncologyWarsawPoland
  4. 4.Department of PathologyM. Sklodowska-Curie Memorial Cancer Center and Institute of OncologyWarsawPoland
  5. 5.Department of Biology and GeneticsMedical University of GdanskGdanskPoland
  6. 6.Department of Molecular BiologyM. Sklodowska-Curie Memorial Cancer Center and Institute of OncologyWarsawPoland
  7. 7.Regional Oncological CenterGdanskPoland
  8. 8.Department of General SurgeryJagiellonian UniversityCracowPoland